Henan Provincial Engineering Laboratory of Insect Bio-Reactor and College of Life Science and Agricultural Engineering, Nanyang Normal University, 1638 Wolong Road, Nanyang 473061, China.
Henan Key Laboratory of Organic Functional Molecule and Drug Innovation, School of Chemistry and Chemical Engineering, Henan Normal University, 46 Jianshe East Road, Xinxiang 453007, China.
Biomolecules. 2024 Mar 14;14(3):350. doi: 10.3390/biom14030350.
Cyclic dinucleotides (CDNs) are cyclic molecules consisting of two nucleoside monophosphates linked by two phosphodiester bonds, which act as a second messenger and bind to the interferon gene stimulating factor (STING) to activate the downstream signaling pathway and ultimately induce interferon secretion, initiating an anti-infective immune response. Cyclic dinucleotides and their analogs are lead compounds in the immunotherapy of infectious diseases and tumors, as well as immune adjuvants with promising applications. Many agonists of pathogen recognition receptors have been developed as effective adjuvants to optimize vaccine immunogenicity and efficacy. In this work, the binding mechanism of human-derived interferon gene-stimulating protein and its isoforms with cyclic dinucleotides and their analogs was theoretically investigated using computer simulations and combined with experimental results in the hope of providing guidance for the subsequent synthesis of cyclic dinucleotide analogs.
环二核苷酸（CDNs）是由两个核苷酸单磷酸通过两个磷酸二酯键连接而成的环状分子，作为第二信使与干扰素基因刺激因子（STING）结合，激活下游信号通路，最终诱导干扰素分泌，引发抗感染免疫反应。环二核苷酸及其类似物是抗感染和抗肿瘤免疫治疗的先导化合物，也是具有广阔应用前景的免疫佐剂。许多病原体识别受体激动剂已被开发为有效的佐剂，以优化疫苗的免疫原性和疗效。在这项工作中，我们使用计算机模拟理论研究了人源干扰素基因刺激蛋白及其同工型与环二核苷酸及其类似物的结合机制，并结合实验结果，希望为后续环二核苷酸类似物的合成提供指导。
